PROJECT SUMMARY/ABSTRACT Globally, nearly 3 billion people rely on solid fuels for cooking and heating, the vast majority in low- and middle- income countries (LMICs). The resulting household air pollution (HAP) is the third leading risk factor in the 2010 global burden of disease, accounting for an estimated 4.3 million deaths annually, largely among women and young children. Previous interventions have provided cleaner biomass-based cookstoves, but have failed to reduce exposure to levels that produce meaningful health improvements. There have been no large-scale field trials with liquefied petroleum gas (LPG) cookstoves, likely the cleanest scalable intervention. Here we propose to conduct a randomized controlled trial of LPG stove and fuel distribution in 3,200 households in four LMICs (India, Guatemala, Peru, and Rwanda) to deliver rigorous evidence regarding potential health benefits across the lifespan. Following a common protocol, each intervention site will recruit 800 pregnant women (aged 18-34 years, <20 weeks gestation), and will randomly assign half their households to receive LPG stoves and a 30-month supply of LPG. Controls will receive the same cookstoves and LPG supply at the end of the study. The mother will be followed along with her child until the child is 2 years old. We estimate that 25% of households will have a second, non-pregnant older adult woman (aged 35-64 years) who will also be enrolled at baseline and followed during the 30-month follow-up period in order to assess cardiopulmonary, metabolic, and cancer outcomes. To optimize intervention use, we will implement behavior change strategies informed by previous experiences and formative research in Year 1. We will assess cookstove use, conduct repeated personal exposure assessments to HAP (PM2.5, black carbon, carbon monoxide), and collect dried blood spots and urinary samples for biomarker analysis and biospecimen storage on all participants at multiple time points. The primary outcomes are low birthweight, pneumonia incidence, and linear growth in the child, and blood pressure in the older adult woman. Secondary outcomes include preterm birth and gross motor development in the child, maternal blood pressure during pregnancy, and endothelial function, respiratory impairment, carcinogenic metabolites, and quality of life in the older adult woman. We will address the following specific aims: (1) using an intent-to-treat analysis, determine the effect of a randomized LPG stove and fuel intervention on health in four diverse LMIC populations using a common protocol; (2) determine the exposure-response relationships for HAP and health; and (3) determine relationships between LPG intervention and both targeted and exploratory biomarkers of exposure/health effects. The proposed trial, powered to detect health effects both within and across four LMIC populations, will provide compelling evidence, including costs and implementation strategies, to inform national and global policies on scaling up LPG stoves among vulnerable populations. Ultimately, this will facilitate deeper policy-level discussions as well as identify requirements for initiating and sustaining HAP interventions globally.